tbuckley/cabot-search huggingface dataset:
Time to treatment in inflammatory breast cancer: Experience from a single institution.
Authors: Alexandra Lopez-Aguiar, Julie Stephens, Akia Clark, Sandy Lee, Ko Un Park
Journal: Journal of Clinical Oncology (2023)

e13530 Background: Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer that accounts for nearly 10% of breast cancer caused mortality. With an annual rate between 1-4% per year and 3-year overall survival (OS) of about 65%, timely completion of trimodal treatment including systemic therapy, surgery, and radiation therapy is essential. Prior studies have demonstrated impact of time to treatment on OS of non-IBC patients. The aim of this study was to examine the relationship between the time from diagnosis to treatment and outcomes for patients with IBC. Methods: Categorically matched patients who underwent treatment of inflammatory and non-inflammatory locally advanced breast cancer at an NCI-Designated Comprehensive Cancer Center from 2006-2016 were analyzed. Clinicopathologic factors were compared using Chi-square and Wilcoxon Rank Sum tests. Overall survival was assessed using Kaplan-Meier methods and log-rank tests. Results: Of 217 patients who underwent excision for breast cancer, 99 had an IBC diagnosis. All patients were female, 85% (n=84) white, and 98% (n=97) had single-sided breast disease. Thirty-one percent (n=31) of patients had clinically node positive (N1) disease, the majority were ER negative (53%), and 38% were HER2 positive. There was no difference in time from first abnormal mammogram to diagnosis between IBC vs non-IBC patients. Ninety-one percent (n=90) of IBC patients underwent neoadjuvant chemotherapy compared to 52% (n=61) of non-IBC patients (p&lt;0.001). Only 27% (n=27) of IBC had a pathological complete response. IBC patients tended to present earlier with symptoms (p=0.054), begin chemotherapy sooner after diagnosis (median days: 10.5 vs 17.0, respectively; p=0.002), and were more likely to receive radiation earlier after surgery (p&lt;0.001). However, IBC patients were also more likely to undergo surgery later (191 vs 153 days; p&lt;0.001) and have a worse OS (p=0.006). While not statistically significant, there was a trend toward worse OS for IBC patients with delayed chemotherapy initiation (p=0.459). Conclusions: IBC is an aggressive form of breast cancer associated with poor OS. Patients with this diagnosis are more likely to receive trimodal therapy sooner, but this may not significantly improve their OS. Further studies are necessary to evaluate effect of time from presentation of initial symptoms to treatment initiation on outcomes.
Treatment (Tx) patterns, efficacy and safety of eribulin for advanced and heavily pretreated breast cancer (ABC): A single-center, real-world study.
Authors: Jin Yang, Jiao Yang, Guangxi Wang, Haochen Zhang, Shidi Zhao, Xiaoai Zhao, Danfeng Dong, Le Wang
Journal: Journal of Clinical Oncology (2023)

e13118 Background: We evaluated the Tx patterns, efficacy and safety of eribulin for heavily pretreated ABC in real-world practice. Methods: Patients (pts) with ABC who had progression on anthracycline/taxane Tx and received eribulin (1.4 mg/m 2 IV on Days 1 and 8 of a 21-day cycle) between April 2020 and August 2022 were enrolled. Response was evaluated using RECIST v1.1. Results: 73 pts were enrolled. Median (range) age was 54 (30–79) years; 78.1% had an Eastern Cooperative Oncology Group (ECOG) performance status (PS) 0–1, and pts had a median of 3 prior lines of chemotherapy. 69.9% of pts had Ki67 &gt;30% and 52.1% had HR+/HER2− disease. 90.4% of pts had visceral metastasis. Eribulin was monotherapy in 28.8% of pts, and combined with bevacizumab, capecitabine, bevacizumab + capecitabine, and anti-HER2 agents in 28.8%, 10.9%, 4.1%, and 27.4%, respectively. The objective response rate was 24.7%; disease control rate was 75.3%. Median progression-free survival (PFS) overall was 6.0 (95% CI, [3.8–8.2]) months (mo). Univariate analysis indicated pts with HER2+ disease had longer PFS than pts with HR+/HER2− or triple-negative BC (median, 8.0, 6.0, and 3.0 mo, respectively; P = 0.049). Pts with Ki67 expression ≤30% had longer PFS than pts with Ki67 &gt;30% (median, 8.0 vs. 4.0 mo; P = 0.024). Pts with late relapse (disease-free survival [DFS] &gt;24 mo) had longer PFS than pts with early recurrence (DFS 6–24 mo) or de novo disease (DFS &lt;6 mo; median PFS, 9.0, 4.5, and 3.6 mo, respectively; P = 0.026). Among 38 pts with HR+/HER2− ABC, pts who received eribulin plus capecitabine had longer PFS than pts who received eribulin monotherapy (median 11.4 vs. 4.0 mo, P = 0.021). Among the 18 pts with a partial response, median PFS was 9.5 mo. Multivariate analysis indicated line of Tx predicted PFS; pts who received eribulin as line 1–3 had longer PFS than pts who received eribulin as line &gt;3 (HR=0.42 [95% CI, 0.19–0.93]; P = 0.034). The most common adverse events were leukopenia (43.2%), anemia (37.9%), and neutropenia (37.8%). Neurotoxicity was rare (2.7%). Conclusions: In this single-center study of pts with heavily pre-treated ABC in China, eribulin Tx resulted in favorable PFS irrespective of molecular subtype, with a manageable safety profile. In pts with a large tumor burden and a good PS, eribulin-based combinations may further improve outcomes. [Table: see text]
Completion rates and trends of the patient-reported outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) across 14 oncology clinical trials.
Authors: Jessica A Emerson, Lindsay Hughes, Kelly Dumais
Journal: Journal of Clinical Oncology (2023)

1579 Background: With growing emphasis on patient-centered regulatory decision making, there is a greater need to incorporate the patient’s voice in oncology clinical trials. Regulatory guidelines outline core patient-reported outcomes (PROs) to include which can inform risk/benefit evaluation. Self-reported symptomatic adverse events (AE) form part of these core PROs, with the new 2023 draft FDA guidance acknowledging the benefits of including them to enhance the assessment of tolerability in early phase dose optimization trials. Given the clinical symptoms and disease burden in oncology, patient burden needs to be thoughtfully considered when incorporating PROs into trials. We assessed trends and feasibility of electronic data collection for symptomatic AEs by analyzing completion compliance and time to complete the Patient-Reported Outcomes version of the Common Terminology Criteria for Adverse Events (PRO-CTCAE) across 14 oncology trials. Methods: All PRO-CTCAE were collected electronically on Clario Tablets. Operational data for completion status (completed or missed) and duration of time to complete the PRO-CTCAE in seconds was extracted. Completion rates over time were examined overall and for every 3-month interval (quarters Q1 to Q9+). The median was selected for analyses of time to complete to account for skewness. Results: The sample included 14 studies across Phase I-III trials across a range of cancers including multiple myeloma, mesothelioma and cancers of the lung, prostate, head/neck, gastric, breast, and ovary. Study durations were 24 weeks and up. The PRO-CTCAE form was completed 13,122 times and missed in 1,182 instances, giving an overall completion rate of 91.7%. On average, 25 questions (range 5-47) covered an average of 13 symptoms (range: 4-25). Completion rate was not associated with the number of questions asked or time since enrollment. The overall median time to complete the PRO-CTCAE was 82s (study-specific median range: 24s to 276s). Examining time to completion as a function of the number of questions revealed a significant positive association, such that each additional question added 5.2 seconds to the time it took to complete the assessment. Conclusions: Completion compliance was high for PRO-CTCAE and remained high regardless of study length and the number of questions included in the PRO-CTCAE form. This suggests that electronic PRO-CTCAE is a feasible solution for collecting self-reported symptomatic AEs. Although time to complete the form increased with the number of questions, results suggest that including a higher number of PRO-CTCAE questions does not negatively impact compliance rate. Our data showing high completion rates may also reflect the benefits of electronic PROs in reducing patient burden and enhancing data quality, as acknowledged by regulatory agencies.
Validation of a 56 gene panel for the detection of somatic variants in metastatic breast cancer.
Authors: Martin Blankfard, Jason H. Christiansen, Nilesh Dharajiya, Ernest Lam, Rick Wenstrup
Journal: Journal of Clinical Oncology (2023)

e13131 Background: The use of ctDNA and next generation sequencing has unprecedented potential to improve genomic profiling and predicting actionable drug treatment in patients with metastatic breast cancer (MBC). Liquid biopsy is uniquely suited for patients where tissue biopsy is not feasible. We specifically focus on actionable variants found in liquid biopsy for MBC including bTMB and MSI. Here we report on the validation of a 56 gene sub panel for the determination of somatic mutations in MBC. Methods: Commercially available, well-characterized, biological ctDNA reference samples with allele frequency ranging from 0.5 -2.5% and bTMB scores (7 – 20) were obtained to analytically evaluate sensitivity, specificity and precision of a range of clinically significant variants (SNV, indels, fusions and copy number variants) in the TSO-500 ctDNA NGS assay. Additionally, 48 Whole blood samples from well characterized metastatic breast cancer patients and 13 healthy donors were obtained from commercial sources. cfDNA was extracted from the plasma separated from whole blood and analyzed on both TS0-500 ctDNA assay and PGDx Elio Complete. TSO-500 ctDNA sequencing data was further analyzed with the DRAGEN pipeline for variant calling and all variants were annotated and curated with the Clinical Genomic Workspace from PierianDx. PGDx utilized a proprietary pipeline and reporting of all variants detected. Results: Analytical validation determined excellent sensitivity (PPA: 99.4 – 100%), specificity (NPA: 99.6 -99.8%) and reproducibility (95 – 98.6%) for SNV, indels, fusions and Copy number variants. bTMB, with a cutoff for bTMB high as &gt;20 mut/Mb, exhibited a sensitivity of 75% and specificity of 93.3%. Limit of detection (LOD) was established at 0.5 % VAF for SNV, Indels and fusions at a minimum read depth of 1000x. LOD for Copy number amplifications was established at 1.26-fold change or 3 copies. Clinical samples also exhibited excellent concordance across both TS0-500 ctDNA and PGDx Elo Complete. SNV, indels and copy number variants exhibited 100% (PPA) sensitivity and 99-100% Specificity (NPA). bTMB exhibited 87.5 % sensitivity and 96.22% specificity. As expected, fusions and microsatellite instability were observed in the clinical population but were rare. No reportable mutations were found in the healthy donors. Actionable mutations were reported for PIK3CA, ESR1, BRCA1 and BRCA2, TP53 and ERBB2 variants. Rare mutations in ATM, CHEC2, PALB2, FGFR1 and CCND1 were also observed. Conclusions: Clinical utility of liquid biopsy assays requires excellent sensitivity, specificity and precision. The Epic 56 gene panel has established clinical validity and high sensitivity and specificity across all relevant variants including bTMB in MBC. This clinically available NGS panel for metastatic breast cancer allows for routine genomic profiling, specifically in patients where tissue biopsy cannot be obtained.
Increasing the study of novel anticancer therapies in adolescents: Facilitating adolescent inclusion in adult research.
Authors: Christina Bucci-Rechtweg, Stergios Zacharoulis, Evgenia Mengou, Solange Corriol-Rohou, Nathalie Gaspar, Christopher Copland
Journal: Journal of Clinical Oncology (2023)

e13654 Background: Adolescent cancer patients are disproportionately excluded from clinical trials due to trial designs with lower age limits set to the legal age of majority. This has led to a persistent time lag between adult and pediatric approval of new medicines. Publication of new US regulatory guidance encourages inclusion of adolescents in disease- and/or target-appropriate adult trials to facilitate earlier adolescent access to effective therapies. To understand impacts of this and other initiatives fostering adolescent inclusion, a review of recent cancer drug approvals was performed by the ACCELERATE Fostering Age Inclusive Research (FAIR) group. FAIR is an international research collaborative whose aim is to reduce adolescent inequities in access to novel anticancer therapies. Methods: A comprehensive analysis of new oncology drug approvals in Europe (EMA) and the US (FDA) will be conducted. EMA and FDA databases will be interrogated to identify all novel anticancer drug approvals and new use approvals (innovator and generic or biosimilar) between 2018 and 2022. Specific sections of drug labels (Indications and Usage, Dosing and Administration, Use in Specific Populations, Clinical Pharmacology, Clinical studies) will be evaluated. The study team will assess: inclusiveness of the Indication for Use statement; applicability of the approved indication to an adolescent cohort. This analysis will be conducted in sequence: phase 1 analyzes the EMA approvals, phase 2 analyzes the FDA approvals, followed by a comparative analysis across the regions. Phase 1 data are presented using descriptive statistics. Results:. Conclusions: This research evaluating new European drug approvals shows a limited number of anticancer therapies have been adequately studied or approved for adolescent use, even when the approved indication is relevant to adolescents. Recent regulatory guidance to promote the inclusion of adolescents in adult oncology drug trials has not yet led to an increase in adolescent labelling. Increasing awareness of medical oncologists and study sponsors may facilitate cultural mindset change, leading to expansion of eligibility criterion to adolescents and shortening the time lag of adolescent access to novel anticancer therapies. [Table: see text]
Global adoption of remote technologies to enable patient-centric oncology clinical trials: Analysis by the Bloomberg New Economy International Cancer Coalition.
Authors: Robert Michael Daly, Otis W. Brawley, Mary K. Gospodarowicz, Olufunmilayo I. Olopade, Ibilola Fashoyin, Victoria Wolodzko Smart, I-Fen Chang, Craig L. Tendler, Geoff Kim, Charles S. Fuchs, Lianshan Zhang, Jeffrey J. Legos, Cristina Duran, Chitkala Kalidas, Jing Qian, Justin Finnegan, Piotr Pilarski, Amy Silverstein, Yi-Long Wu, Bob T. Li
Journal: Journal of Clinical Oncology (2023)

1584 Background: Fewer than 5% of patients with cancer enroll in a clinical trial, partly due to the significant financial and logistical burden on patients, especially among underserved populations. The COVID-19 pandemic marked a significant shift in the adoption of remote technologies and decentralized trial operations by major pharmaceutical companies. We sought to determine the current global state of adoption of these technologies, understand factors that are driving or preventing adoption of them, and highlight aspirations and direction for industry to enable more patient-centric trials. Methods: The multi-stakeholder Bloomberg New Economy International Cancer Coalition composed of patient advocacy, industry, government regulators, and academic medical centers developed a survey directed to global biopharmaceutical companies of the Coalition with a focus on registrational clinical trials. The survey was organized into three main sections: 1) Impact of different remote monitoring and data collection technologies on patient-centricity; 2) Adoption of these technologies in oncology and all therapeutic areas; 3) Barriers/facilitators to adoption. Results: Administered from October 1 to December 31, 2022, a total of 8 companies completed the survey (response rate: 100%), representing 33% of oncology market by revenues in 2021. Across nearly all remote monitoring and data collection technologies, adoption in oncology trials lags that of all trials. In the current state, eDiary/eCOA is the most utilized technology with 56% and 51% adoption for all trials and oncology trials, respectively, whereas visits in local physician networks is the least adopted at 12% and 7%, respectively. Looking forward, the difference between the current and aspired adoption rate in 5 years for oncology is large, with respondents expecting a 40% or greater absolute adoption increase in 8 out of the 11 technologies (Table). Furthermore, respondents identified digitally enabled recruitment, local or mobile imaging capabilities, and local physician networks as those technologies that would be most impactful for improving patient centricity in the long term. Conclusions: This survey is the first by a coalition of global stakeholders to determine the current state and future aspirations for the use of remote technologies in oncology clinical trials. These efforts may galvanize momentum towards greater adoption of enabling technologies supporting a new paradigm of trials that are more accessible, less burdensome, and more inclusive.[Table: see text]
Treatment patterns and clinical outcomes of newly diagnosed early-stage and locally advanced triple negative breast cancer (TNBC): A retrospective cohort analysis of national real-world data in England.
Authors: Manpreet Barham, Dionysios Ntais, Karen Macey, Kirsty Murray, Catherine Castillo, Alexander Ford, Amisha Patel, Tim Holbrook
Journal: Journal of Clinical Oncology (2023)

e12577 Background: TNBC patients have poorer survival outcomes when compared to other types of breast cancer, due to the lack of treatment options available and the aggressiveness of the disease. The current standard of care for early-stage TNBC is neoadjuvant pembrolizumab in combination with chemotherapy followed by pembrolizumab monotherapy after surgery (KEYNOTE-522), however prior to this treatment options and outcomes have been relatively limited compared to hormone receptor- and HER2- positive breast cancers. This study aimed to describe the treatment patterns and clinical outcomes of early-stage and locally advanced TNBC patients in England before the approval of KEYNOTE-522. Methods: In this retrospective cohort study, data from the English National Cancer Registration and Analysis Service databases (Cancer Registry, Systemic Anti-Cancer Therapy, Hospital Episode Statistics [HES], National Radiotherapy Dataset and Diagnostic Imaging Dataset) were used. Adults with a first record of primary early-stage or locally advanced TNBC (stage II – IIIb) between 01/01/2015 and 31/12/2018 were indexed. Treatment pathways and clinical outcomes were investigated over a maximum of 5-years follow-up period extending to December 2020. Outcomes were described descriptively. Results: A total of 3,475 patients met the inclusion criteria for the newly diagnosed TNBC cohort. 82.7% and 17.3% of patients were diagnosed at stage II and stage III respectively and, 83.3% were of white ethnicity, and 46.6% were node positive. Around 80% of patients had a primary surgery performed (i.e. a mastectomy or breast conserving surgery). Anthracyclines were the most common drug type used as a first regimen in both the neoadjuvant and adjuvant settings. During the follow up period, 37.7% and 15.3% of patients experienced locoregional or distant metastatic progression, respectively and 22.6% died. Median OS or EFS was not reached as &lt; 50% patients died within the 5-year follow up period. The 5-year OS and EFS rate was ~57% and ~60%, respectively. Increased healthcare resource utilisation (HCRU) with associated high costs was reported in the time periods post diagnosis. The mean number of TNBC-related inpatient stays was the highest in the 3 to 6 months following index; 3.77 (SD = 3.95), costing a total of £4,992,150.48 (per patient cost: £1,458.84 [£1918.76], mean [SD]). Conclusions: This is the first real world evidence study using the England NCRAS datasets to assess the outcomes of the early-stage and locally advanced TNBC population in England. Treatment plans were heterogenous in TNBC patients and probability of survival was poor. This highlights the need for improvement of the treatment options and thus clinical outcomes of this patient population.
Glioblastoma in elderly patients: A retrospective analysis of survival and response based on molecular and clinical characteristics—Experience in our centre.
Authors: Estibaliz Iza, Joan Manel Mañe, Eluska Iruarrizaga, Itziar Rubio, Ricardo Fernandez, Pablo Jiménez, Failah Mohamed Lamin, Mikel Toquero, Alberto Muñoz
Journal: Journal of Clinical Oncology (2023)

e14054 Background: Glioblastoma (GBM) is the most lethal and the most common malignant central nervous system tumor in adults. The standard treatment includes surgery, radiotherapy (Rt) and temozolomide based chemotherapy (Qt). However, compared with younger population, overall survival (OS) is worse in elderly patients and, additionally, this group is not usually included in clinical trials. Retrospective studies have shown, among other factors, tumor biology and performance status with poorer survival in older population, but it is necessary further research in order to discover prognostic factors and optimize management in this group. Methods: In this retrospective study we analyzed clinical and tumor biology characteristics in older population (≥ 70 years) and we also compared these results with younger population (&lt; 70 years) for the purpose of enhance clinical outcomes. From November-2016 to October-2022, we analyzed 111 patients in our hospital: group A (&lt; 70 years): 80 patients, group B (≥ 70 years): 31 patients. The tumor biology and patient characteristics are described in the table. Results: OS was statistically better in group A (A 13.93 +/- 1.28 months versus B 9.39 +/- 1.45 months; p=0.035). In contrast of A, in B no differences in OS were observed related with type of surgery (p=0.78), MGMT status (p=0.4) or p53 status (p=0.75). However, significant differences in OS were observed in B in multivariate analysis according to modality of adjuvant treatment (greater OS in Qt-Rt+ Qt &gt; Qt-Rt &gt; Rt exclusively &gt; no treatment; p&lt;0.001) and performance status (greater OS in PS 0 &gt; PS 1 &gt; PS 2 &gt; PS 3; p=0.001). There was no differences of OS between A and B if the adjuvant treatment was concomitant Qt-Rt +/- Qt (p=0.81), but with this therapy there was a toxic death (infection Grade 5) in B group. Other relevant toxicities Grade 3/4 in this group with Qt-Rt +/-Qt were: infection 3.2%, thrombocytopenia 12.9%, neutropenia 12.9%, leukopenia 6.45%, anemia 3.2%, thrombosis 3.2% Conclusions: Temozolomide based therapy is an effective and safe option for the treatment of patients ≥ 70 years with GBM. We need to perform prospective trials in this population in order to recognize prognostic and predictive factors to allow better treatment selection.[Table: see text]